Pyrido- pyridazino indole

This indole C-7 Heck cyclization strategy was employed by Shao and Cai in a synthesis of anhydrolycorine-7-one from the requisite N-aroylindoline [275], by Miki in syntheses of pratosine and hippadine from substrates like 262 [276], and by Rigby to synthesize anhydrodehydrolycorine from an N-benzylhydroindolone [277, 278]. Thai and co-workers constructed examples of the new ring systems, pyrido[2 ,3-d ]pyridazino[2,3-a]indole (264) and pyrido[2 ,3 -Heck cyclizations on the appropriate 2-bromopyridine precursors (e.g., 263) at C-2 or C-7, respectively [279, 280]. Compound 264 undergoes oxidative-addition with methyl acrylate at the C-3 position. This resulting product (not shown) can also be obtained from 263 in a tandem Heck sequence with methyl acrylate (62% yield). 

Examples of migratory insertion to aromatic rings also include the total syntheses of anhydrolycorine-7-one (217) [102] and the f-azaebutnane series [103]. As illustrated in Scheme 38, an intramolecular Heck reaction of Af-acylindoline 216 installed the six-membered lactam in anhydrolycorine-7-one (217). In a similar process, the tetracyclic pyrido-[2 ,3 -prepared from bromopyridine 218 under phase-transfer catalysis conditions. Pyridyl indole 219 is a precursor of the pentacyclic skeleton of the E-azaeburnane series. 

Heck Annulation. PolyheterocyUc systems such as pyrido[2, 3 -t( ]pyridazino[2,3-fljindoles 291 are available by Heck annulation reactions using nicotinyl-indole substrates (Scheme 100). ... 

Italian researchers synthesized a new class of DNA intercalators [53], based on the four core containing system of pyridazino-[r,6 l,2]-pyrido[4,3-b]-indole (163, Scheme 23). Compoimds 163-165 were used in the form of... 

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